Lina Ma1, Wen Dong2, Rong Wang3, Yun Li4, Baolei Xu5, Jingshuang Zhang2, Zhiwei Zhao2, Yulan Wang2. 1. Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China; Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China. 2. Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China. 3. Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China. Electronic address: rong_wang72@aliyun.com. 4. Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China. 5. Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Abstract
AIMS: To determine the effects and underlying molecular mechanisms of caloric restriction (CR) in C57BL/6 mice. METHODS: Thirty-six 6-week-old male C57BL/6 mice were assigned to a normal control group (NC, n=12), a high energy group (HE, n=12), and a CR group (n=12), and received a normal diet, a high-calorie diet, or a calorie-restricted diet, respectively, for 44 weeks. Body weight and serum glucose concentration were regularly recorded, and animals were sacrificed and hippocampus tissues were collected for immunohistochemistry (n=6 per group), western blotting (n=3 per group) and real-time polymerase chain reaction (n=3 per group) analysis at the end of the 44-week experimental period. Immunohistochemistry, western blotting and real-time polymerase chain reaction were used to detect changes in hippocampal proteins may be involved in the SIRT1/mTOR pathways. RESULTS: Body weight and serum glucose over the 44 weeks in animals from the CR group were lower than those of HE group. The number of SIRT1-immunoreactive cells in the CR group was significantly higher than in the NC and HE groups, and SIRT1 mRNA expression in the CR group was significantly higher than that in the HE group, but there was no difference in SIRT1 protein expression among the three groups. mTOR and S6K1 protein activation and mTOR and S6K1 mRNA were significantly lower in the CR group than in the NC group. CONCLUSIONS: Our findings suggest that a CR diet could lead to activation of SIRT1 and suppression of mTOR and S6K1 activation in C57BL/6 mice. We have shown that the SIRT1/mTOR signaling pathways may be involved in the neuroprotective effect of CR.
AIMS: To determine the effects and underlying molecular mechanisms of caloric restriction (CR) in C57BL/6 mice. METHODS: Thirty-six 6-week-old male C57BL/6 mice were assigned to a normal control group (NC, n=12), a high energy group (HE, n=12), and a CR group (n=12), and received a normal diet, a high-calorie diet, or a calorie-restricted diet, respectively, for 44 weeks. Body weight and serum glucose concentration were regularly recorded, and animals were sacrificed and hippocampus tissues were collected for immunohistochemistry (n=6 per group), western blotting (n=3 per group) and real-time polymerase chain reaction (n=3 per group) analysis at the end of the 44-week experimental period. Immunohistochemistry, western blotting and real-time polymerase chain reaction were used to detect changes in hippocampal proteins may be involved in the SIRT1/mTOR pathways. RESULTS: Body weight and serum glucose over the 44 weeks in animals from the CR group were lower than those of HE group. The number of SIRT1-immunoreactive cells in the CR group was significantly higher than in the NC and HE groups, and SIRT1 mRNA expression in the CR group was significantly higher than that in the HE group, but there was no difference in SIRT1 protein expression among the three groups. mTOR and S6K1 protein activation and mTOR and S6K1 mRNA were significantly lower in the CR group than in the NC group. CONCLUSIONS: Our findings suggest that a CR diet could lead to activation of SIRT1 and suppression of mTOR and S6K1 activation in C57BL/6 mice. We have shown that the SIRT1/mTOR signaling pathways may be involved in the neuroprotective effect of CR.
Authors: Larissa S Celiberto; Franziska A Graef; Genelle R Healey; Else S Bosman; Kevan Jacobson; Laura M Sly; Bruce A Vallance Journal: Immunology Date: 2018-05-16 Impact factor: 7.397